Durvalumab + Chemotherapy for Mesothelioma

(DREAM3R Trial)

Recruiting at 56 trial locations

Overseen By Stephanie Winata- International Sites

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: PrECOG, LLC.

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Autoimmune disorders, Brain metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 19

Duration: 12-18 weeks

214 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on systemic corticosteroids or other immunosuppressive medications, you may need to stop them at least 28 days before starting the trial treatment.

What data supports the effectiveness of the drug combination Durvalumab and chemotherapy for treating mesothelioma?

Research shows that combining Durvalumab with chemotherapy improved survival in patients with mesothelioma, with a median survival of 20.4 months compared to 12.1 months with standard chemotherapy alone. This combination has shown promising clinical activity and is supported by genomic and immune analyses indicating better outcomes for certain patients. ^{1 2 3 4 5}

Is the combination of Durvalumab and chemotherapy safe for humans?

The combination of Durvalumab with chemotherapy has been studied in trials for mesothelioma and other cancers, showing that side effects are consistent with known chemotherapy side effects, and any side effects from the immunotherapy were mild (grade 2 or lower). This suggests that the treatment is generally safe for humans. ^{1 2 3 4 5}

How is the drug combination of Durvalumab, Ipilimumab, and Nivolumab with chemotherapy unique for treating mesothelioma?

This drug combination is unique because it combines immune checkpoint inhibitors, which help the immune system attack cancer cells, with standard chemotherapy, potentially improving survival rates in mesothelioma patients compared to chemotherapy alone. ^{1 3 4 6 7}

What is the purpose of this trial?

Patients with pleural mesothelioma (PM) that cannot be surgically removed will receive standard chemotherapy (cisplatin or carboplatin and pemetrexed) given with durvalumab, a type of immunotherapy, or a treatment chosen by the study doctor, which is either standard chemotherapy or immunotherapy combination (ipilimumab and nivolumab). Durvalumab is an antibody (a type of human protein) that works by blocking a body substance called Programmed Death-Ligand 1 (PD-L1). Blocking PD-L1 helps the body's immune system attack cancer cells. Research has shown that durvalumab can slow tumor growth and shrink tumors in some people with cancer. Previous studies of combining durvalumab and chemotherapy showed that this combination is active in advanced mesothelioma. The purpose of this study is to see whether adding durvalumab to standard chemotherapy will improve overall survival (OS) in patients with PM.

Research Team

Patrick Forde, MD

Principal Investigator

Johns Hopkins University

Anna Nowak, MD

Principal Investigator

Faculty of Health and Medical Sciences University of Western Australia

Eligibility Criteria

Adults over 18 with epithelioid pleural mesothelioma that can't be removed by surgery. They should have a good performance status, weigh more than 30 kg, and have acceptable blood test results. Women must not be pregnant and use contraception; men also need to follow certain contraceptive guidelines.

Inclusion Criteria

Life expectancy of at least 12 weeks.

Willing and able to comply with all study requirements, including treatment, timing and/or nature of required assessments.

I am an adult diagnosed with a type of cancer called epithelioid pleural mesothelioma that cannot be removed by surgery.

Exclusion Criteria

My diagnosis was confirmed with a fine needle biopsy.

I have hearing loss or nerve issues that prevent me from taking certain medications.

I do not have active brain cancer symptoms or uncontrolled brain metastases.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive durvalumab with standard chemotherapy or physician's choice of treatment for 4 to 6 cycles

12-18 weeks

Every 3 weeks

Maintenance

Participants in the experimental arm receive durvalumab every 4 weeks until disease progression, unacceptable toxicity, or withdrawal

Until disease progression

Every 4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Every 12 weeks

Treatment Details

Interventions

• Durvalumab
• Ipilimumab and Nivolumab
• Standard Chemotherapy

Trial Overview The trial is testing if adding durvalumab (an immunotherapy drug) to standard chemotherapy improves survival in patients with advanced pleural mesothelioma compared to standard chemotherapy alone or combined with other immunotherapies like ipilimumab and nivolumab.

Participant Groups

Group I: Experimental Arm: Durvalumab + Chemotherapy, then Durvalumab Maintenance Experimental Treatment 1 Intervention

Durvalumab + Standard Chemotherapy for 4 to 6 cycles, followed by Maintenance with Durvalumab

Group II: Control Arm: Chemotherapy, then Observation Active Control 1 Intervention

Standard Chemotherapy for 4 to 6 cycles, followed by Observation

Group III: Control Arm: Ipilimumab and Nivolumab Active Control 1 Intervention

Ipilimumab every 6 weeks and Nivolumab every 2 or 3 weeks for up to 2 years.

Durvalumab is already approved in European Union, United States, Japan for the following indications:

Approved in European Union as Imfinzi for:

• Locally advanced, unresectable non-small cell lung cancer (NSCLC)

Approved in United States as Imfinzi for:

• Extensive-stage small cell lung cancer (ES-SCLC)
• Limited-stage small cell lung cancer (LS-SCLC)
• Locally advanced or metastatic urothelial carcinoma

Approved in Japan as Imfinzi for:

• Not specified in provided sources

Who Is Running the Clinical Trial?

PrECOG, LLC.

Lead Sponsor

Trials

19

Recruited

8,000+

Thoracic Oncology Group Australasia (TOGA)

Collaborator

Trials

1

Recruited

210+

University of Sydney

Collaborator

Trials

208

Recruited

417,000+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

The phase 2 PrE0505 trial demonstrated that the combination of the anti-PD-L1 antibody durvalumab with platinum-pemetrexed chemotherapy significantly improved overall survival in patients with unresectable pleural mesothelioma, achieving a median survival of 20.4 months compared to 12.1 months with historical controls.

The treatment was generally safe, with adverse events consistent with chemotherapy and no severe immunotherapy-related side effects, while genomic analyses suggested that a higher mutation burden and diverse T cell repertoire were associated with better clinical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial. Forde, PM., Anagnostou, V., Sun, Z., et al.[2022]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

Nivolumab (Opdivo) combined with ipilimumab (Yervoy) has been approved by the FDA as a first-line treatment for adults with unresectable malignant pleural mesothelioma, based on promising results from the CHECKMATE 743 trial.

The approval was supported by an interim analysis comparing the combination therapy to standard chemotherapy, indicating that this new treatment option may offer better outcomes for patients with this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approves Nivolumab Plus Ipilimumab for Previously Untreated Unresectable Malignant Pleural Mesothelioma. Wright, K.[2021]

Nivolumab combined with ipilimumab has been approved by the FDA as the first-line treatment for unresectable malignant pleural mesothelioma (MPM), showing improved overall survival (OS) of 18.1 months compared to 14.1 months for chemotherapy, based on a study of 605 patients.

The treatment was particularly more beneficial for patients with non-epithelioid histology, and the approval process involved collaboration with multiple international health agencies, marking the first new drug regimen for MPM since 2004.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Nivolumab in Combination with Ipilimumab for the Treatment of Unresectable Malignant Pleural Mesothelioma. Nakajima, EC., Vellanki, PJ., Larkins, E., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Durvalumab with platinum-pemetrexed for unresectable pleural mesothelioma: survival, genomic and immunologic analyses from the phase 2 PrE0505 trial. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Protocol of DREAM3R: DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma-a phase 3 randomised trial. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Durvalumab with first-line chemotherapy in previously untreated malignant pleural mesothelioma (DREAM): a multicentre, single-arm, phase 2 trial with a safety run-in. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

FDA Approves Nivolumab Plus Ipilimumab for Previously Untreated Unresectable Malignant Pleural Mesothelioma. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Nivolumab in Combination with Ipilimumab for the Treatment of Unresectable Malignant Pleural Mesothelioma. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Meta-Analysis on the Combination of Chemotherapy With Programmed Death-Ligand 1 and Programmed Cell Death Protein 1 Blockade as First-Line Treatment for Unresectable Pleural Mesothelioma. [2023]